PROMINENT ROLE OF SECONDARY ANCHOR RESIDUES IN PEPTIDE BINDING TO HLA-A2.1 MOLECULES
PROMINENT ROLE OF SECONDARY ANCHOR RESIDUES IN PEPTIDE BINDING TO HLA-A2.1 MOLECULES
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DOI：
10.1016/0092-8674(93)90472-3
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发表时间：
1993-09-10
期刊：
影响因子：
64.5
通讯作者：
SETTE, A
中科院分区：
文献类型：
--
作者：
RUPPERT, J;SIDNEY, J;SETTE, A
利用定量分子结合分析和化学合成的天然表位文库，对组织相容性白细胞抗原(HLA)-A2.1-多肽相互作用的功能决定因素进行了详细的研究。证实了位置2和C末端负的疏水锚定残基的重要性。这些锚对于高亲和力结合是必要的，但不是充分的，因为仅基于这些锚的预测只有30%左右的准确性。还展示了其他几个职位(1、3和7)的重要作用。这些残基在多肽中的位置与先前由X射线结晶学证明的二级A2.1口袋相匹配。从功能的角度来看，非异构体和十聚体中的带电残基对结合的显性负效应相似，而非异构体和十聚体中的正效应不同。考虑到二级锚定的扩展基序将2.1结合表位的可预测性提高到70%的水平，突显了扩展基序的实用价值。
The functional determinants of histocompatibility leukocyte antigen (HLA)-A2.1-peptide interactions have been detailed by the use of quantitative molecular binding assays and a chemically synthesized library of naturally occurring epitopes. The importance of hydrophobic anchor residues in position 2 and the C-terminus minus was confirmed. These anchors are necessary, but not sufficient, for high affinity binding, as the predictions based solely on these anchors are only about 30% accurate. Prominent roles for several other positions (1, 3, and 7) were also demonstrated. The location of these residues within the peptides matches secondary A2.1 pockets previously demonstrated by X-ray crystallography. From a functional standpoint, similar dominant negative effects on binding were observed for charged residues in both nonamers and decamers, while positive effects differed between nonamers and decamers. An extended motif taking into account secondary anchors increased the predictability of A2.1-binding epitopes to a level of 70%, underscoring the practical usefulness of extended motifs.